Cyclin-dependent kinases (CDKs) and their associated cyclins are key regulators of cell cycle progression. Caenorhabditis elegans has two predicted A- type cyclins, encoded by the genes cya-1 and cya-2. Cyclin A has been shown to be required for...

A sustainable energy future is critical for environmental and strategic reasons. One alternative to petroleum used for transportation is ethanol derived from cellulosic biomass. The major barrier for biomass conversion is a cost effective method...

Chronic low back pain is a debilitating and devastating disease affecting millions of people worldwide. Considerable evidence indicates that there are sex-related differences in clinical and experimental pain sensitivity in men and women. Women...

The demand for novel molecularly targeted drugs will continue to rise as we make progress toward personalizing cancer treatments to the molecular signatures of individual tumors. While the collection and analysis of genomic data has become routine,...

MicroRNA-10b (miR-10b) is considered a marker of disease aggressiveness in pancreatic ductal adenocarcinoma (PDAC), in view of the fact that lower levels of miR-10b are associated with better response to neoadjuvant therapy, likelihood of surgical...

Molecular optical imaging in vivo has potential for functional assessment of tumor tissue at the cellular and subcellular level. Advances in biological understanding of genomics and proteomics have increased the knowledge of possible cellular...

In utero exposure to maternal malnutrition is associated with increase offspring susceptibility to cardiometabolic and neuropsychiatric disease. Epigenetic mechanisms mediate, at least in part, fetal adaptations to adverse in utero environments...

RNA binding proteins are fundamental components of crucial biological processes in all domains of life. The development of techniques to study RNA binding protein complexes is, therefore, broadly impactful. I employed multiple genome-wide...

Despite the array of targeted therapeutics that currently exist to combat breast cancer, disease progression leading to metastasis, and tumor recurrence still remains a significant clinical challenge. Efforts to identify novel pathways and...

The overarching goal of this thesis was two-fold. First, to determine if the effects of chronic anabolic androgenic steroid (AAS) treatment on anxiety-like behaviors are sex-specific and second to determine how different environmental modulators...

Nerve growth factor (NGF), the prototypic neurotrophin, is well characterized for its pro-survival and growth effects in sympathetic and sensory neurons. Acting as a target-derived factor, NGF regulates the maturation of innervating neurons, and...

Swarming motility is a flagella-dependent surface motility, and is also a form of bacterial group behavior. Similar to its counterpart biofilm formation, our understanding of swarming motility has been hampered by its complex set of requirements...

Increased fetal hemoglobin (HbF) expression is beneficial for [beta]-hemoglobinopathy patients; however, most inducing agents do not possess the ideal combination of efficacy, safety and availability. Better understanding the mechanisms involved in...

In the nervous system, neuronal communication relies critically on the function of membrane ion channels. One of these is the voltage-gated sodium channel (VGSC), which is essential for the generation and propagation of action potentials in...

Candida albicans is a fungal species that naturally exists as a commensal member of the human microbiota, but can assume a pathogenic lifestyle and subsequently induce life-threatening systemic infections. The ability of the fungus to grow in...

The objective of this thesis was to examine the neural and physiological substrates underlying the processing of aversive information, and how individual differences in anxiety influence these responses. In a series of experiments, we utilized skin...

Three types of Fc receptors for IgG, FcyRI (CD64), FcyRII (CD32), and FcyRIII (CD 16) are expressed differentially on blood leukocytes. In particular, CD64 and CD32 are constitutively expressed on mononuclear phagocytes of the human myeloid system....

Synthetic oleanane triterpenoids (SO) are a novel class of therapeutic compounds based on the structure of oleanolic acid. These synthetic oleanane triterpenoids which include 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), CDDO-methyl...

During an immune reaction to an invading pathogen, a population of lymphocytes with receptors that specifically recognize the pathogen are activated and become memory cells. Characteristically, memory lymphocytes persist for long periods of time...

The circadian clock of the filamentous fungus, Neurospora crassa, consists of a frequency-white-collar ( frq-wc ) based and transcription-translation-derived oscillator. Negative feedback regulation is essential for the oscillatory process, in...

Testicular germ cell tumors (TGCTs) are highly curable with cisplatin-based therapy. The p53 tumor suppressor is induced in response to a variety of cellular stresses. Our previous work has implicated an important role for p53 in TGCT...

Aneuploidy is frequently detected in human cancers and is implicated in carcinogenesis. Pharmacological targeting of aneuploidy is an attractive therapeutic strategy, as this would preferentially eliminate malignant over normal cells. Our prior...

CD4+ T cells are critical for the control of virus infections, memory cell formation and immune surveillance. Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus are two γ-herpesviruses identified in humans and are strongly associated...

Many kinds of cancer, and almost universally metastatic cancer, are refractory to treatment by conventional methods: surgery, radiation, and non-specific cytotoxic chemotherapy. The dawn of the age of personalized medicine presaged 15 years ago...

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia in the aging population. Currently, there is no cure for AD. The hallmark of AD consists of extracellular amyloid plaques, mainly composed...

Despite immunogenicity, melanoma-specific vaccines have demonstrated minimal clinical efficacy in patients with established disease, but enhance survival when administered in the adjuvant setting. It has been shown that T cell infiltration of...

The phenomenon of immunological memory has been known for thousands of years. This knowledge has been applied to vaccination, which has resulted in a dramatic reduction in the number of deaths due to infectious diseases. Immunological memory is...

Protein secretion is executed by the secretory pathway, which involves the delivery of membrane and soluble secretory proteins in vesicle intermediates that capture newly-synthesized proteins assembled in the endoplasmic reticulum (ER) and then...

All cells must organize their cytoplasm in order to carry out functions properly and survive in different environments, and the requirement for organization is increased in large, multinucleate cells. It has long been known that membrane-bound...

How the genome is shaped directly influences how it is expressed. In fact, the genome is organized at many different levels, each imparting specific regulation over transcription. Fundamental principles regulating genome organization are poorly...

IL-1β is a potent proinflammatory cytokine produced in response to Pseudomonas aeruginosa infection. While it is appreciated that IL-1β is a critical modulator of the host response to P. aeruginosa infection, the host and bacterial determinants...

Systemic sclerosis (SSc) is a rare and often-fatal systemic autoimmune disease characterized by vasculature dysfunction, immune activation, and extracellular matrix deposition in skin and internal organs. The etiology of SSc is unknown, but it is...

Mutations in the Drosophila retinal-specific Phospholipase C (NORPA) cause massive retinal degeneration within five days of constant light exposure. We have previously shown that in norpA mutants persistent complexes between the light receptor...

The ectomycorrhizal symbiosis between temperate forest trees and some soil fungi is an adaptation to resource limitations of both symbionts. Nitrogen enrichment of historically N-limited forest ecosystems may change this symbiosis through direct...

Sepsis is a worldwide problem with an annual mortality rate reaching as high as 45%. Understanding its pathogenesis and the innate immune response to infection is key to the development of new treatments. CD163, a monocyte/macrophage-specific...

Since acyl Co-A: cholesterol acyltransferase (ACAT) is believed to be involved in important physiological functions such as lipoprotein assembly, cholesterol absorption, steroidogenesis, and pathogenesis of atherosclerosis, ACAT has been studied...

Evolutionary Computation (EC) is one of the most advanced computational techniques. It has been frequently and successfully used to find good solutions to many complicated optimization problems with limited computational resources. EC is the...